The possibility of developing more precise methods of detecting and diagnosing cancer by identifying and characterizing tumour-associated antigens (i.e. antigens expressed by tumours) is of great medical interest.
Monoclonal antibodies against tumour-associated antigens may play an important role for the detection of cancer because of their greater specificity. To date most of the monoclonal antibodies raised against cancer-associated antigens have been of mouse origin, being expressed by hybridomas resulting from a fusion of spleen cells from a mouse immunized with a human cancer cell line or cells from a cancer patient with a mouse myeloma cell line. Immunogenicity in the mouse is a requirement for antigens recognized by murine monoclonal antibodies and they do not necessarily correspond to antigens recognized by human antibodies. In addition, the therapeutic value of these murine monoclonal antibodies may be limited since patients recognize these antibodies as foreign proteins and may therefore develop an adverse immune response against the murine antibody. The result may be a neutralization of the therapeutic effect and triggering of potentially dangerous allergic reactions.
Human hybridoma antibodies may be more promising as diagnostic and therapeutic agents for administration to patients with cancer under the assumption that human monoclonal antibodies are less immunogenic in humans than heterologous antibodies and are capable of recognizing the relevant antigens.
Problems related to the specificity of murine monoclonal anti-tumour antibodies are illustrated by the colon adenocarcinoma antibody 17-A1, which has been used in diagnosis and therapy, but has now been found to react with normal as well as tumour tissue (Hybridoma 5 Suppl. 1, 1986, special issue on Ca-17-A1, ed. Z. Steplewski).
The immune response in patients against administered murine monoclonal antibody has been described by numerous investigators (e.g. H. F. Sears et al., Lancet 1985, i:762-765; and M. S. Mitchell et al., Prog. Cancer Res. Ther. 21, 1982, Raven Press, New York).
Colo-rectal cancer is one of the most frequently occurring cancers and one of the major causes of death from cancer. The prognosis of this cancer type has not improved for a long period of time, and novel methods for the detection of colo-rectal cancer and adjuvant therapy concomitantly with surgery thereof are therefore needed.
Therefore, a need exists for a human carcinoma tumour-associated antigen, in particular one which is substantially not expressed by normal tissue, and antibodies against such an antigen for diagnostic and therapeutic purposes.